胰腺癌是高致死率恶性肿瘤,找到特异的生物标志物对揭示胰腺癌发展机制及精准治疗有重要意义。仅在人和鼠中,Tspan8在胰腺表达,但作用尚不明确。我们研究发现:Tspan8/CD151促进胰腺癌转移且功能互补;敲低Tspan8/CD151减弱胰腺癌侵袭性及干细胞迁移性;携带Tspan8/CD151的胰腺癌干细胞外泌体增强细胞迁移性;外泌体通过分子信息传递调控胰腺癌转移。据此,申请人提出"Tspan8/CD151通过肿瘤干细胞外泌体促进胰腺癌转移"。本课题拟:从分子、细胞水平验证携带Tspan8/CD151干细胞外泌体增强胰腺癌侵袭性;质谱技术分析Tspan8/CD151对外泌体运载蛋白的影响;用Tspan8/CD151敲基因小鼠,探究其通过外泌体促进胰腺癌转移的功能和作用。本研究将从携带Tspan8/CD151的胰腺癌干细胞外泌体这个新视角,为阐明胰腺癌转移机制及精准治疗胰腺癌提供新思路。

Pancreatic cancer is a malignant tumor with a high mortality rate. The most crucial problem for revealing the pathology and treating is to find specific biomarkers. Only in humans and rats, Tspan8 is expressed in the pancreas. Our previous studies have found that: pancreatic cancer-derived exosomes promote metastasis; knockdown the expression of Tspan8/CD151 could decrease the proliferation of pancreatic cancer stem cells、the invasion of the pancreatic cancer cells and the ability of delivery; Exosomes help metastasis by degrading the ECM. Based on these findings, we propose that "Tspan8/CD151 regulates the invasiveness of cancer cells through cancer stem cell-derived exosomes in pancreatic cancer metastasis." This project intends to: 1. co-culture pancreatic cancer stem cell-derived exosomes with pancreatic cancer cells to verify the promotion of exosomes on the migration and invasion of pancreatic cancer cells; 2. analysis the impaction of Tspan8/CD151 on exosome composition by MALDI-TOF Mass Spectrometry; 3. observe and clarify the function and mechanism of Tspan8 and/or CD151 knockdown pancreatic cancer stem cell-derived exosomes on pancreatic cancer. The completion of this project is expected to provide a new perspective for elucidating the mechanism of pancreatic cancer metastasis and treating pancreatic cancer precisely by accurately blocking the transmission of pancreatic cancer stem cells-derived exosomal information.